scholarly journals Autism sensory dysfunction in an evolutionarily conserved system

2018 ◽  
Vol 285 (1893) ◽  
pp. 20182255 ◽  
Author(s):  
Greta Vilidaite ◽  
Anthony M. Norcia ◽  
Ryan J. H. West ◽  
Christopher J. H. Elliott ◽  
Francesca Pei ◽  
...  

There is increasing evidence for a strong genetic basis for autism, with many genetic models being developed in an attempt to replicate autistic symptoms in animals. However, current animal behaviour paradigms rarely match the social and cognitive behaviours exhibited by autistic individuals. Here, we instead assay another functional domain—sensory processing—known to be affected in autism to test a novel genetic autism model in Drosophila melanogaster . We show similar visual response alterations and a similar development trajectory in Nhe3 mutant flies (total n = 72) and in autistic human participants (total n = 154). We report a dissociation between first- and second-order electrophysiological visual responses to steady-state stimulation in adult mutant fruit flies that is strikingly similar to the response pattern in human adults with ASD as well as that of a large sample of neurotypical individuals with high numbers of autistic traits. We explain this as a genetically driven, selective signalling alteration in transient visual dynamics. In contrast to adults, autistic children show a decrease in the first-order response that is matched by the fruit fly model, suggesting that a compensatory change in processing occurs during development. Our results provide the first animal model of autism comprising a differential developmental phenotype in visual processing.

2018 ◽  
Author(s):  
Greta Vilidaite ◽  
Anthony M. Norcia ◽  
Ryan J. H. West ◽  
Christopher J. H. Elliott ◽  
Francesca Pei ◽  
...  

AbstractThere is increasing evidence for a strong genetic basis for autism, with many genetic models being developed in an attempt to replicate autistic symptoms in animals. However, current animal behaviour paradigms rarely match the social and cognitive behaviours exhibited by autistic individuals. Here we instead assay another functional domain – sensory processing – known to be affected in autism to test a novel genetic autism model in Drosophila melanogaster. We show similar visual response alterations and a similar development trajectory in Nhe3 mutant flies (total N=72) and in autistic human participants (total N=154). We report a dissociation between first- and second-order electrophysiological visual responses to steady-state stimulation in adult mutant fruit flies that is strikingly similar to the response pattern in human adults with ASD as well as that of a large sample of neurotypical individuals with high numbers of autistic traits. We explain this as a genetically driven, selective signalling alteration in transient visual dynamics. In contrast to adults, autistic children show a decrease in the first-order response that is matched by the fruit fly model, suggesting that a compensatory change in processing occurs during development. Our results provide the first animal model of autism comprising a differential developmental phenotype in visual processing.


2015 ◽  
Vol 112 (40) ◽  
pp. E5523-E5532 ◽  
Author(s):  
Peter T. Weir ◽  
Michael H. Dickinson

Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to behavioral context. We imaged panneuronal responses to visual stimuli in a highly conserved central brain region in the fruit fly, Drosophila, during flight. In one substructure, the fan-shaped body, automated analysis revealed three layers that were unresponsive in quiescent flies but became responsive to visual stimuli when the animal was flying. The responses of these regions to a broad suite of visual stimuli suggest that they are involved in the regulation of flight heading. To identify the cell types that underlie these responses, we imaged activity in sets of genetically defined neurons with arborizations in the targeted layers. The responses of this collection during flight also segregated into three sets, confirming the existence of three layers, and they collectively accounted for the panneuronal activity. Our results provide an atlas of flight-gated visual responses in a central brain circuit.


1997 ◽  
Vol 78 (3) ◽  
pp. 1373-1383 ◽  
Author(s):  
Marc M. Umeno ◽  
Michael E. Goldberg

Umeno, M. M. and Goldberg, M. E. Spatial processing in the monkey frontal eye field. I. Predictive visual responses. J. Neurophysiol. 78: 1373–1383, 1997. Neurons in the lateral intraparietal area and intermediate layers of the superior colliculus show predictive visual responses. They respond before an impending saccade to a stimulus that will be brought into their receptive field by that saccade. In these experiments we sought to establish whether the monkey frontal eye field had a similar predictive response. We recorded from 100 presaccadic frontal eye field neurons (32 visual cells, 48 visuomovement cells, and 20 movement cells) with the use of the classification criteria of Bruce and Goldberg. We studied each cell in a continuous stimulus task, where the monkey made a saccade that brought a recently appearing stimulus into its receptive field. The latency of response in the continuous stimulus task varied from 52 ms before the saccade to 272 ms after the saccade. We classified cells as having predictive visual responses if their latency in the continuous stimulus task was less than the latency of their visual on response to a stimulus in their receptive or movement field as described in a visual fixation task. Thirty-four percent (11 of 32) of the visual cells, 31% (15 of 48) of the visuomovement cells, and no (0 of 20) movement cells showed a predictive visual response. The cells with predictive responses never responded to the stimulus when the monkey did not make the saccade that would bring that stimulus into the receptive field, and never discharged in association with that saccade unless it brought a stimulus into the receptive field. The response in the continuous stimulus task was almost always weaker than the visual on response to a stimulus flashed in the receptive field. Because cells with visual responses but not cells with movement activity alone showed the effect, we conclude that the predictive visual response is a property of the visual processing in the frontal eye field, i.e., a response to the stimulus in the future receptive field. It is not dependent on the actual planning or execution of a saccade to that stimulus. We suggest that the predictive visual mechanism is one in which the brain dynamically calculates the spatial location of objects in terms of desired displacement. This enables the oculomotor system to perform in a spatially accurate manner when there is a dissonance between the retinal location of a target and the saccade necessary to acquire that target. This mechanism does not require an explicit calculation of target position in some supraretinal coordinatesystem.


1996 ◽  
Vol 76 (5) ◽  
pp. 2872-2885 ◽  
Author(s):  
Y. Trotter ◽  
S. Celebrini ◽  
B. Stricanne ◽  
S. Thorpe ◽  
M. Imbert

1. The influence of viewing distance on disparity selectivity was investigated in area V1 of behaving monkeys. While the animals performed a fixation task, cortical cells were recorded extracellularly in the foveal representation of the visual field. Disparity selectivity was assessed by using static random dot stereograms (RDSs) through red/green filters flashed over the central fixation target. To determine the influence of the viewing distance, a color video monitor was positioned at fixed distances of 20, 40, or 80 cm. The same RDSs with the same angular size of dots were used at the three distances. 2. Disparity sensitivity was tested on 139 cells, of which 78 were analyzed at two or more distances and the rest (61) at a single distance. When disparity selectivity was analyzed at a given distance, about half the cells were found to be selective at 40 or 80 cm, but only a third at 20 cm. Near cells were > or = 1.5 times more common than far cells at all three distances. The latency distribution of the responses of disparity-selective (DS) cells was similar at all three distances, with a mean distribution centered around 60 ms. 3. Changing the viewing distance drastically affected the neural activity of the V1 neurons. The visual responsiveness of 60 of 78 cells (77%) was significantly changed. Disparity selectivity could be present at a given distance and absent at other(s), with often a loss of visual response. This emergence of disparity coding was the strongest effect (28 of 78 or 36%) and occurred more frequently from short to long distances. Among the cells that remained disparity insensitive at all recorded distances (31 of 78 or 40%), about half also showed modulations of the amplitude of the visual response. For cells that remained DS at all recorded distances (13 of 78 or 17%), changing the viewing distance also affected the sharpness (or magnitude) of disparity coding in terms of level of visual responsiveness and those changes were often combined with variations in tuning width. In only two cells did the peak of selectivity type change. Finally, the activity of four DS cells was not affected at all by the viewing distance. 4. Another effect concerned the level of ongoing activity (OA), defined as being the neural activity in darkness preceding the flash of the visual stimulus while the monkey was fixating the small bright target. Changing the viewing distance resulted in significant changes in OA level for more than half of the cells (41 of 78 or 53%). The most common effect was an increase in OA level at the shorter distance. The modulations of both visual responsiveness and OA could occur simultaneously, although they often had opposite signs. Indeed, the two effects were statistically independent of each other, i.e., modulations of visual responses were not related to the level of excitability of the neurons. 5. Control experiments were performed that showed that the effects of changing the viewing distance were not due to the retinal patterns in that the modulations of visual responsiveness were independent of the dot density. Seventeen cells were also tested for a possible effect of vergence by the use of prisms. When there was an effect of distance, it could be closely or partially reproduced by using prisms. These controls, together with the effects observed on OA, strongly suggest that the modulations of neural activity of the V1 neurons by the viewing distance are extraretinal in origin, probably proprioceptive. 6. The modulation of visual responsiveness by the viewing distance in the primary visual cortex indicates that integration of information from both retinal and extraretinal sources can occur early in the visual processing pathway for cortical representation of three-dimensional space. A functional scheme of three-dimensional cortical circuitry is discussed that shows cortical areas where disparity selectivity and modulations of visual activity by the angle of gaze have been described so far.


1998 ◽  
Vol 79 (6) ◽  
pp. 3272-3278 ◽  
Author(s):  
Matthew T. Schmolesky ◽  
Youngchang Wang ◽  
Doug P. Hanes ◽  
Kirk G. Thompson ◽  
Stefan Leutgeb ◽  
...  

Schmolesky, Matthew T., Youngchang Wang, Doug P. Hanes, Kirk G. Thompson, Stefan Leutgeb, Jeffrey D. Schall, and Audie G. Leventhal. Signal timing across the macaque visual system. J. Neurophysiol. 79: 3272–3278, 1998. The onset latencies of single-unit responses evoked by flashing visual stimuli were measured in the parvocellular (P) and magnocellular (M) layers of the dorsal lateral geniculate nucleus (LGNd) and in cortical visual areas V1, V2, V3, V4, middle temporal area (MT), medial superior temporal area (MST), and in the frontal eye field (FEF) in individual anesthetized monkeys. Identical procedures were carried out to assess latencies in each area, often in the same monkey, thereby permitting direct comparisons of timing across areas. This study presents the visual flash-evoked latencies for cells in areas where such data are common (V1 and V2), and are therefore a good standard, and also in areas where such data are sparse (LGNd M and P layers, MT, V4) or entirely lacking (V3, MST, and FEF in anesthetized preparation). Visual-evoked onset latencies were, on average, 17 ms shorter in the LGNd M layers than in the LGNd P layers. Visual responses occurred in V1 before any other cortical area. The next wave of activation occurred concurrently in areas V3, MT, MST, and FEF. Visual response latencies in areas V2 and V4 were progressively later and more broadly distributed. These differences in the time course of activation across the dorsal and ventral streams provide important temporal constraints on theories of visual processing.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefano Rozzi ◽  
Marco Bimbi ◽  
Alfonso Gravante ◽  
Luciano Simone ◽  
Leonardo Fogassi

AbstractThe ventral part of lateral prefrontal cortex (VLPF) of the monkey receives strong visual input, mainly from inferotemporal cortex. It has been shown that VLPF neurons can show visual responses during paradigms requiring to associate arbitrary visual cues to behavioral reactions. Further studies showed that there are also VLPF neurons responding to the presentation of specific visual stimuli, such as objects and faces. However, it is largely unknown whether VLPF neurons respond and differentiate between stimuli belonging to different categories, also in absence of a specific requirement to actively categorize or to exploit these stimuli for choosing a given behavior. The first aim of the present study is to evaluate and map the responses of neurons of a large sector of VLPF to a wide set of visual stimuli when monkeys simply observe them. Recent studies showed that visual responses to objects are also present in VLPF neurons coding action execution, when they are the target of the action. Thus, the second aim of the present study is to compare the visual responses of VLPF neurons when the same objects are simply observed or when they become the target of a grasping action. Our results indicate that: (1) part of VLPF visually responsive neurons respond specifically to one stimulus or to a small set of stimuli, but there is no indication of a “passive” categorical coding; (2) VLPF neuronal visual responses to objects are often modulated by the task conditions in which the object is observed, with the strongest response when the object is target of an action. These data indicate that VLPF performs an early passive description of several types of visual stimuli, that can then be used for organizing and planning behavior. This could explain the modulation of visual response both in associative learning and in natural behavior.


Author(s):  
Emme O’Rourke ◽  
Emily L. Coderre

AbstractWhile many individuals with autism spectrum disorder (ASD) experience difficulties with language processing, non-linguistic semantic processing may be intact. We examined neural responses to an implicit semantic priming task by comparing N400 responses—an event-related potential related to semantic processing—in response to semantically related or unrelated pairs of words or pictures. Adults with ASD showed larger N400 responses than typically developing adults for pictures, but no group differences occurred for words. However, we also observed complex modulations of N400 amplitude by age and by level of autistic traits. These results offer important implications for how groups are delineated and compared in autism research.


1994 ◽  
Vol 72 (3) ◽  
pp. 1220-1226 ◽  
Author(s):  
D. Czepita ◽  
S. N. Reid ◽  
N. W. Daw

1. Cats were reared in the dark to 3, 5, and 11 mo. We studied the N-methyl-D-aspartate (NMDA) receptor contribution to the visual response in the cortex, defined as the percentage reduction in visual response after application of 2-amino-5-phosphonovaleric acid (APV). We also studied the firing rate in response to the optimal visual stimulus and the spontaneous activity. We made comparisons of all these properties between light-reared and dark-reared animals. 2. The NMDA receptor contribution to the visual response in layers IV, V, and VI of dark-reared animals was substantially above that in light-reared animals at all ages tested. 3. The specificity of receptive field properties in dark-reared animals showed some degeneration between 6 wk and 3 mo of age. At > or = 3 mo, almost no cells were specific for orientation and direction of movement. 4. Firing rate was lower in dark-reared animals at all ages, suggesting a decrease in excitatory drive to the visual cortex. 5. Spontaneous activity was equal in dark- and light-reared animals, suggesting that the overall level of activity (including visual responses as well as spontaneous activity) in light-reared animals is higher than in dark-reared animals. This should tend to upregulate glutamate receptors in general in dark-reared animals.


2020 ◽  
Author(s):  
Adrian Schütz ◽  
Vishal Bharmauria ◽  
Xiaogang Yan ◽  
Hongying Wang ◽  
Frank Bremmer ◽  
...  

SummaryVisual landmarks influence spatial cognition [1–3], navigation [4,5] and goal-directed behavior [6–8], but their influence on visual coding in sensorimotor systems is poorly understood [6,9–11]. We hypothesized that visual responses in frontal cortex control gaze areas encode potential targets in an intermediate gaze-centered / landmark-centered reference frame that might depend on specific target-landmark configurations rather than a global mechanism. We tested this hypothesis by recording neural activity in the frontal eye fields (FEF) and supplementary eye fields (SEF) while head-unrestrained macaques engaged in a memory-delay gaze task. Visual response fields (the area of visual space where targets modulate activity) were tested for each neuron in the presence of a background landmark placed at one of four oblique configurations relative to the target stimulus. 102 of 312 FEF and 43 of 256 SEF neurons showed spatially tuned response fields in this task. We then fit these data against a mathematical continuum between a gaze-centered model and a landmark-centered model. When we pooled data across the entire dataset for each neuron, our response field fits did not deviate significantly from the gaze-centered model. However, when we fit response fields separately for each target-landmark configuration, the best fits shifted (mean 37% / 40%) toward landmark-centered coding in FEF / SEF respectively. This confirmed an intermediate gaze / landmark-centered mechanism dependent on local (configuration-dependent) interactions. Overall, these data show that external landmarks influence prefrontal visual responses, likely helping to stabilize gaze goals in the presence of variable eye and head orientations.HighlightsPrefrontal visual responses recorded in the presence of visual landmarksResponse fields showed intermediate gaze / landmark-centered organizationThis influence depended on specific target-landmark configurations


2000 ◽  
Vol 17 (2) ◽  
pp. 283-289 ◽  
Author(s):  
K.E. BINNS ◽  
T.E. SALT

In the rat, the superficial gray layer (SGS) of the superior colliculus receives glutamatergic projections from the contralateral retina and from the visual cortex. A few fibers from the ipsilateral retina also directly innervate the SGS, but most of the ipsilateral visual input is provided by cholinergic afferents from the opposing parabigeminal nucleus (PBG). Thus, visual input carried by cholinergic afferents may have a functional influence on the responses of SGS neurones. When single neuronal extracellular recording and iontophoretic drug application were employed to examine this possibility, cholinergic agonists were found to depress responses to visual stimulation. Lobeline and 1-acetyl-4-methylpiperazine both depressed visually evoked activity and had a tendency to reduce the background firing rate of the neurones. Carbachol depressed the visual responses without any significant effect on the ongoing activity, while the muscarinic receptor selective agonist methacholine increased the background activity of the neurones and reduced their visual responses. Lobeline was chosen for further studies on the role of nicotinic receptors in SGS. Given that nicotinic receptors are associated with retinal terminals in SGS, and that the activation of presynaptic nicotinic receptors normally facilitates transmitter release (in this case glutamate release), the depressant effects of nicotinic agonists are intriguing. However, many retinal afferents contact inhibitory neurones in SGS; thus it is possible that the increase in glutamate release in turn facilitates the liberation of GABA which goes on to inhibit the visual responses. We therefore attempted to reverse the effects of lobeline with GABA receptor antagonists. The depressant effects of lobeline on the visual response could not be reversed by the GABAA antagonist bicuculline, but the GABAB antagonist CGP 35348 reduced the effects of lobeline. We hypothesize that cholinergic drive from the parabigeminal nucleus may activate presynaptic nicotinic receptors on retinal terminals, thereby facilitating the release of glutamate onto inhibitory neurones. Consequently GABA is released, activating GABAB receptors, and thus the ultimate effect of nicotinic receptor activation is to depress visual responses.


Sign in / Sign up

Export Citation Format

Share Document